Pediatric Oncology, Princess Máxima Center, Utrecht, the Netherlands.
Department of Hospital Pharmacy, Erasmus Medical Center, Rotterdam, the Netherlands.
JCO Precis Oncol. 2023 Jun;7:e2200678. doi: 10.1200/PO.22.00678.
Dexamethasone, the preferred corticosteroid in most treatment protocols for pediatric acute lymphoblastic leukemia (ALL), can induce undesirable side effects. Neurobehavioral and sleep problems are frequently reported, but the interpatient variability is high. We therefore aimed to identify determinants for parent-reported dexamethasone-induced neurobehavioral and sleep problems in pediatric ALL.
Our prospective study included patients with medium-risk ALL and their parents during maintenance treatment. Patients were assessed before and after one 5-day dexamethasone course. Primary end points were parent-reported dexamethasone-induced neurobehavioral and sleep problems, measured with the Strengths and Difficulties Questionnaire and Sleep Disturbance Scale for Children, respectively. Analyzed determinants included patient and parent demographics, disease and treatment characteristics, parenting stress (Parenting Stress Index and Distress Thermometer for Parents), dexamethasone pharmacokinetics, and genetic variation (candidate single-nucleotide polymorphisms and ). Statistically significant determinants identified in univariable logistic regression analyses were incorporated in a multivariable model.
We included 105 patients: median age was 5.4 years (range, 3.0-18.8) and 61% were boys. Clinically relevant dexamethasone-induced neurobehavioral and sleep problems were reported by parents in 70 (67%) and 61 (59%) patients, respectively. In our multivariable regression models, we identified parenting stress as a significant determinant for parent-reported neurobehavioral (odds ratio [OR], 1.16; 95% CI, 1.07 to 1.26) and sleep problems (OR, 1.06; 95% CI, 1.02 to 1.10). Furthermore, parents who experienced more stress before start of a dexamethasone course reported more sleep problems in their child (OR, 1.16; 95% CI, 1.02 to 1.32).
We identified parenting stress, and not dexamethasone pharmacokinetics, genetic variation, patient/parent demographics, or disease/treatment characteristics, as a significant determinant for parent-reported dexamethasone-induced neurobehavioral and sleep problems. Parenting stress may be a modifiable target to reduce these problems.
地塞米松是大多数儿科急性淋巴细胞白血病（ALL）治疗方案中首选的皮质类固醇，但会引起不良的副作用。神经行为和睡眠问题经常被报道，但个体间的差异很大。因此，我们旨在确定小儿 ALL 中父母报告的地塞米松诱导的神经行为和睡眠问题的决定因素。
我们的前瞻性研究包括中危 ALL 患儿及其父母在维持治疗期间。患者在一个 5 天的地塞米松疗程前后进行评估。主要终点是父母报告的地塞米松诱导的神经行为和睡眠问题，分别用《长处与困难问卷》和《儿童睡眠障碍量表》进行测量。分析的决定因素包括患者和父母的人口统计学、疾病和治疗特征、养育压力（父母养育压力指数和父母压力温度计）、地塞米松药代动力学和遗传变异（候选单核苷酸多态性和）。在单变量逻辑回归分析中确定的有统计学意义的决定因素被纳入多变量模型。
我们纳入了 105 名患者：中位年龄为 5.4 岁（范围，3.0-18.8），61%为男孩。父母报告 70 名（67%）和 61 名（59%）患儿出现有临床意义的地塞米松诱导的神经行为和睡眠问题。在我们的多变量回归模型中，我们发现养育压力是父母报告的神经行为（优势比[OR]，1.16；95%可信区间，1.07 至 1.26）和睡眠问题（OR，1.06；95%可信区间，1.02 至 1.10）的显著决定因素。此外，在开始地塞米松疗程前经历更多压力的父母报告他们的孩子有更多的睡眠问题（OR，1.16；95%可信区间，1.02 至 1.32）。
我们确定养育压力，而不是地塞米松药代动力学、遗传变异、患者/父母人口统计学或疾病/治疗特征，是父母报告的地塞米松诱导的神经行为和睡眠问题的显著决定因素。养育压力可能是减少这些问题的一个可调节的目标。
